| ribose-5-phosphate isomerase | |||||||
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| Identifiers | |||||||
| EC number | 5.3.1.6 | ||||||
| CAS number | 9023-83-0 | ||||||
| Databases | |||||||
| IntEnz | IntEnz view | ||||||
| BRENDA | BRENDA entry | ||||||
| ExPASy | NiceZyme view | ||||||
| KEGG | KEGG entry | ||||||
| MetaCyc | metabolic pathway | ||||||
| PRIAM | profile | ||||||
| PDB structures | RCSB PDB PDBe PDBsum | ||||||
| Gene Ontology | AmiGO / EGO | ||||||
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Ribose-5-phosphate isomerase (Rpi) is an enzyme that catalyzes the conversion between ribose-5-phosphate (R5P) and ribulose-5-phosphate (Ru5P).
Contents |
In the reaction, the overall consequence is the movement of a carbonyl group from carbon number 1 to carbon number 2; this is achieved by the reaction going through an enediol intermediate (Figure 1).[1] Through site-directed mutagenesis, Asp87 of spinach RpiA was suggested to play the role of a general base in the interconversion of R5P to Ru5P.[2]
Rpi exists as two distinct proteins forms, termed RpiA and RpiB. Although RpiA and RpiB catalyze the same reaction, they show no sequence or overall structural homology.2 According to Jung et al.,[3] an assessment of RpiA using SDS-PAGE shows that the enzyme is a homodimer of 25 kDa subunits. The molecular weight of the RpiA dimer was found to be 49 kDa [3] by gel filtration. Recently, the crystal structure of RpiA was determined. (please see http://www3.interscience.wiley.com/cgi-bin/fulltext/97516673/PDFSTAR)
Due to its role in the pentose phosphate pathway and the Calvin cycle, RpiA is highly conserved in most organisms, such as bacteria, plants, and animals. RpiA plays an essential role in the metabolism of plants and animals, as it is involved in the Calvin cycle which takes place in plants, and the pentose phosphate pathway which takes place in plants as well as animals.
In the non-oxidative part of the pentose phosphate pathway, RpiA converts Ru5P to R5P which then is converted by ribulose phosphate 3-epimerase to xylulose-5-phosphate (figure 3). The end result of the reaction essentially is the conversion of the pentose phosphates to intermediates used in the glycolytic pathway. In the oxidative part of the pentose phosphate pathway, RpiA converts Ru5P to the final product, R5P through the isomerization reaction (figure 3). The oxidative branch of the pathway is a major source for NADPH which is needed for biosynthetic reactions and protection against reactive oxygen species.[4]
In the Calvin cycle, the energy from the electron carriers is used in carbon fixation, the conversion of carbon dioxide and water into carbohydrates. RpiA is essential in the cycle, as Ru5P generated from R5P is subsequently converted to ribulose-1,5-bisphosphate (RuBP), the acceptor of carbon dioxide in the first dark reaction of photosynthesis (Figure 3).[5] The direct product of RuBP carboxylase reaction is glyceraldehyde-3-phosphate; these are subsequently used to make larger carbohydrates.[6] Glyceraldehyde-3-phosphate is converted to glucose which is later converted by the plant to storage forms (e.g., starch or cellulose) or used for energy.
Ribose-5-phosphate isomerase deficiency is mutated in a rare disorder, Ribose-5-phosphate isomerase deficiency
RpiA generated attention when the enzyme was found to play an essential role in the pathogenesis of the parasite Plasmodium falciparum, the causative agent of malaria. Plasmodium cells have a critical need for a large supply of the reducing power of NADPH via PPP in order to support their rapid growth. The need for NADPH is also required to detoxify heme, the product of hemoglobin degradation.[7] Furthermore, Plasmodium has an intense requirement for nucleic acid production to support its rapid proliferation. The R5P produced via increased pentose phosphate pathway activity is used to generate 5-phospho-D-ribose α-1-pyrophosphate (PRPP) needed for nucleic acid synthesis. It has been shown that PRPP concentrations are increased 56 fold in infected erythrocytes compared with uninfected erythrocytes.[8] Hence, designing drugs that target RpiA in Plasmodium falciparum could have therapeutic potential for patients that suffer from malaria.
As of late 2007, 15 structures have been solved for this class of enzymes, with PDB accession codes 1LK5, 1LK7, 1LKZ, 1M0S, 1NN4, 1O1X, 1O8B, 1UJ4, 1UJ5, 1UJ6, 1USL, 1XTZ, 2BES, 2BET, and 2F8M.